Inhibitory influence of phosphate and arsenate on contraction of skinned skeletal and cardiac muscle

Nosek, Thomas M.; Leal‐Cardoso, J. H.; McLaughlin, Mark; Godt, R. E.

doi:10.1152/ajpcell.1990.259.6.c933

Cited by 59 publications

(67 citation statements)

References 26 publications

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“…18 It has been shown that the effects of P i and pH on isometric force are independent in cardiac muscle. 2,13,19 Our results are in agreement with these studies because the product of the relative reductions in force by 30 mmol/L P i and pH 6.2 separately did not significantly differ from the combined effect found under simulated ischemic conditions (30 mmol/L P i , pH 6.2).…”

Section: Combined Effects Of P I and Phsupporting

confidence: 91%

Effects of Calcium, Inorganic Phosphate, and pH on Isometric Force in Single Skinned Cardiomyocytes From Donor and Failing Human Hearts

et al. 2001

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Background-During ischemia, the intracellular calcium and inorganic phosphate (P i ) concentrations rise and pH falls. We investigated the effects of these changes on force development in donor and failing human hearts to determine if altered contractile protein composition during heart failure changes the myocardial response to Ca 2ϩ , P i , and pH. Methods and Results-Isometric force was studied in mechanically isolated Triton-skinned single myocytes from left ventricular myocardium. Force declined with added P i to 0.33Ϯ0.02 of the control force (pH 7.1, 0 mmol/L P i ) at 30 mmol/L P i and increased with pH from 0.64Ϯ0.03 at pH 6.2 to 1.27Ϯ0.02 at pH 7.4. Force dependency on P i and pH did not differ between donor and failing hearts. Incubation of myocytes in a P i -containing activating solution caused a potentiation of force, which was larger at submaximal than at maximal [Ca 2ϩ ]. Ca 2ϩ sensitivity of force was similar in donor hearts and hearts with moderate cardiac disease, but in end-stage failing myocardium it was significantly increased. The degree of myosin light chain 2 phosphorylation was significantly decreased in end-stage failing compared with donor myocardium, resulting in an inverse correlation between Ca 2ϩ responsiveness of force and myosin light chain 2 phosphorylation. Conclusions-Our results indicate that contractile protein alterations in human end-stage heart failure alter Ca

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Section: Combined Effects Of P I and Phsupporting

confidence: 91%

Effects of Calcium, Inorganic Phosphate, and pH on Isometric Force in Single Skinned Cardiomyocytes From Donor and Failing Human Hearts

et al. 2001

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“…Interestingly, the contractile properties of cardiac muscle preparations appear to be more sensitive to added P i than those of skeletal muscle preparations. For instance, Nosek et al (29) reported that 10 mM added P i decreased cardiac muscle force ϳ60% compared with a 40% force decline in skeletal muscle preparations in the same study. We also observed that force declined ϳ65% in the cardiac myocyte preparation in response to 10 mM added P i .…”

Section: Discussionmentioning

confidence: 76%

Inorganic phosphate speeds loaded shortening in rat skinned cardiac myocytes

Hinken¹,

McDonald²

2004

American Journal of Physiology-Cell Physiology

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Hinken, Aaron C., and Kerry S. McDonald. Inorganic phosphate speeds loaded shortening in rat skinned cardiac myocytes. Am J Physiol Cell Physiol 287: C500 -C507, 2004. First published April 14, 2004 10.1152/ajpcell.00049.2004.-Force generation in striated muscle is coupled with inorganic phosphate (Pi) release from myosin, because force falls with increasing P i concentration ([Pi]). However, it is unclear which steps in the cross-bridge cycle limit loaded shortening and power output. We examined the role of Pi in determining force, unloaded and loaded shortening, power output, and rate of force development in rat skinned cardiac myocytes to discern which step in the cross-bridge cycle limits loaded shortening. Myocytes (n ϭ 6) were attached between a force transducer and position motor, and contractile properties were measured over a range of loads during maximal Ca 2ϩ activation. Addition of 5 mM Pi had no effect on maximal unloaded shortening velocity (V o) (control 1.83 Ϯ 0.75, 5 mM added P i 1.75 Ϯ 0.58 muscle lengths/s; n ϭ 6). Conversely, addition of 2.5, 5, and 10 mM P i progressively decreased force but resulted in faster loaded shortening and greater power output (when normalized for the decrease in force) at all loads greater than ϳ10% isometric force. Peak normalized power output increased 16% with 2.5 mM added P i and further increased to a plateau of ϳ35% with 5 and 10 mM added P i. Interestingly, the rate constant of force redevelopment (ktr) progressively increased from 0 to 10 mM added Pi, with k tr ϳ360% greater at 10 mM than at 0 mM added Pi. Overall, these results suggest that the P i release step in the cross-bridge cycle is rate limiting for determining shortening velocity and power output at intermediate and high relative loads in cardiac myocytes. muscle mechanics; force-velocity relationship; cross-bridge cycle DURING MUSCLE CONTRACTION myosin cross bridges cyclically interact with actin in a process that is driven energetically by hydrolysis of ATP. The chemomechanical states in the crossbridge cycle have been investigated extensively in skinned muscle fiber preparations, and the transition rates between these states are qualitatively similar to rates derived from muscle protein studies in solution (15). A working model for the chemomechanical steps in the cross-bridge cycle is shown in Fig. 1 (40), which is based on extensive work in the field (for reviews see Refs. 3 and 15). According to this model, the transition from weak-binding, non-force-generating cross bridges to strong-binding, forcegenerating states is associated with the release of inorganic phosphate (P i ) (steps 3-5, Fig. 1; Ref. 16). Force generation is maintained through the release of ADP (step 6, Fig. 1; Refs. 6 and 22), which is followed by binding of ATP and subsequent cross-bridge detachment. The binding of ATP and its hydrolysis are thought to be relatively fast processes in skinned fibers (9,14,23). Thus the rate-limiting step in the cross-bridge cycle is thought to occur after ATP hydrolysis, either during an ...

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“…There seems to be agreement that Pi reduces force by reducing the number of cross-bridges in high-force-producing states (Pate & Cooke, 1989;Dantzig et al 1992 (Nosek, Fender & Godt, 1987;Nosek, Leal-Cardoso, McLaughlin & Godt, 1990). However, others have failed to see synergism even in fast-twitch fibres (Chase & Kushmerick, 1988;Pate & Cooke, 1989).…”

Section: Reduction Of Maximum Isometric Forcementioning

confidence: 99%

Muscle cell function during prolonged activity: cellular mechanisms of fatigue

Dg¹,

Lännergren²,

Westerblad³

1995

Experimental Physiology

292

283

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Muscle performance declines during prolonged and intense activity; important components are a reduction in force production and shortening velocity and a prolongation of relaxation. In this review we consider how the changes in metabolites (particularly H+, inorganic phosphate (Pi), ATP and ADP) and changes in sarcoplasmic reticulum Ca2+ release lead to the observed changes in force, shortening velocity and relaxation. The reduced force is caused by a combination of reduced maximum force‐generating capacity, reduced myofibrillar Ca2+ sensitivity and reduced Ca2+ release. The reduced maximum force and Ca2+ sensitivity are largely explained by the effects of H+ and Pi that have been observed in skinned fibres. At least three different forms of reduced Ca2+ release can be recognized but the mechanisms involved are incompletely understood. The reduced shortening velocity can be partly explained by the effects of H+ that have been observed in skinned fibres. In addition it is proposed that ADP, which depresses shortening velocity, increases during contractions to a level that is considerably higher than existing measurements suggest. Changes in Ca2+ release are probably unimportant for the reduced shortening velocity. The prolongation of relaxation can arise both from slowing of the rate of decline of myoplasmic calcium concentration and from slowing of cross‐bridge detachment rates. A method of analysis which separates these components is described. The increase in H+ and the other metabolite changes during fatigue can independently affect both components. Finally we show that reduced force, shortening velocity and slowed relaxation all contribute to the decline in muscle performance during a working cycle in which the muscle first shortens actively and then is stretched passively by an antagonist muscle.

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Inhibitory influence of phosphate and arsenate on contraction of skinned skeletal and cardiac muscle

Cited by 59 publications

References 26 publications

Effects of Calcium, Inorganic Phosphate, and pH on Isometric Force in Single Skinned Cardiomyocytes From Donor and Failing Human Hearts

Effects of Calcium, Inorganic Phosphate, and pH on Isometric Force in Single Skinned Cardiomyocytes From Donor and Failing Human Hearts

Inorganic phosphate speeds loaded shortening in rat skinned cardiac myocytes

Muscle cell function during prolonged activity: cellular mechanisms of fatigue

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